tbuckley/cabot-search huggingface dataset:
Abstract 15616: Single Cell Transcriptomic Profiling Identifies Ferroptosis and Oxidative Stress as Potential Drivers of Muscle Dysfunction in Pad
Authors: Lillian Tran, Ricardo Ferrari, Bowen Xie, Edwyn Assaf, Ulka Sachdev
Journal: Circulation (2022)

Introduction: Peripheral artery disease (PAD) affects &gt;8 million people nationwide and is disabling. PAD-associated myopathy causes weakness yet is understudied. Unbiased transcriptomic profiling of muscle satellite cells (MuSC) which drive recovery may elucidate the etiology of ischemic myopathic change. Hypothesis: MuSC in PAD differentially express injury associated pathways that may be novel targets for intervention to reduce ischemic myopathy. Methods: Muscle tissue biopsies were obtained during lower extremity amputation or bypass in PAD/ischemic (N=4; ABI&lt;0.6) and perfused conditions (N=4). CD56+ magnetic assisted cell sorting (MACS)-purified MuSCs were processed for single-cell RNA sequencing using the 10X Genomics platform. Unsupervised clustering and differential gene expression were performed. Western blot (WB) informed by transcriptomics confirmed pathway activation in perfused, ischemic and PAD(-) cells. Results: Among 25,298 analyzed ischemic and perfused cells, a unique cluster of MuSC transcriptionally programmed for apoptosis was detected under chronically ischemic PAD but not control conditions. Furthermore, quiescent cells with renewal capacity were lower in MuSC from ischemic muscle (17.8% vs. 26.3%, P =0.03) while pathologic myofibroblasts were almost exclusively seen in PAD (Fig.1A-B). Genes associated with iron metabolism (FTL, FTH), ferroptosis regulation (GSS), oxidative stress (HMOX) and the damage associated molecular pattern (DAMP) HMGB1 were upregulated in ischemic MuSC shown in violin plots (Fig.1C). By WB, CISD1 protein which regulates ferroptosis was elevated in PAD (p &lt;0.03Fig.1C). Conclusions: The data implicate oxidative damage and iron-mediated programmed cell death as potential mechanisms driving muscle dysfunction from chronic ischemia. Targeting ferroptosis and oxidative stress represent novel ways to improve outcomes by reducing myopathy in PAD.
Abstract 14448: On-Table Extubation Associated With Lower Resource Utilization and Non-Inferior Outcomes After Coronary Bypass
Authors: Stacey Telenson, Fady K Soliman, Ronald Vertsman, Benjamin Basseri, Antonio Chiricolo, Enrique Pantin, Anthony Lemaire, Hirohisa Ikegami, Mark J Russo, Leonard Y Lee
Journal: Circulation (2022)

Introduction: Minimizing the duration of postoperative ventilation facilitates early discharge from the intensive care unit (ICU) thus promoting enhanced recovery after cardiac surgery (ERAS). Hence, we sought to investigate the impact of on-table extubation on outcomes and resource utilization after coronary artery bypass graft (CABG) surgery. Methods: We performed a retrospective review of a prospectively collected local database, including all patients undergoing CABG surgery at a large academic center from January 2020 to December 2021. Patients were stratified into two groups, on-table (before leaving the operating room) extubation versus early (&lt; 6 hours after procedure) extubation. In-hospital mortality and postoperative complications were compared using univariate analyses. Length of stay (LOS), 30-day readmission and high resource utilization (HRU), a binary outcome defined as direct procedure cost of the highest quartile, were investigated. Results: A total of 691 patients were included in our analysis, 267 (38.6%) of which were extubated on-table. The two groups had similar median age and preoperative ejection fractions. However, on-table extubation patients were more likely to be males (86.9% vs 76.6%, p&lt;0.001) with smaller BMIs (27.7% vs 28.5%, p=0.002), lower STS risk scores (0.75% vs 0.95%, p=0.022) and lower cerebrovascular disease prevalence (8.2% vs 14.2%, p=0.017). Compared to early extubation, on-table extubation patients had similar rates of in-hospital mortality (0 % vs 1.4 %, p=0.051), postoperative blood transfusion (7.5% vs 9.0%, p=0.494), reintubation (2.6% vs 3.5%, p=0.499) and pneumonia (1.9% vs 3.3%, p=0.263). As hypothesized, on-table extubation patients had shorter ICU LOS (32hrs vs 39hrs, p=0.02), shorter postoperative LOS (4.9 days vs 5.9 days, p=0.003), and lower incidence of high resource utilization (18.0% vs 29.5%, p&lt;0.001). ICU readmission (3.8% vs 3.5%, p=0.887) and 30-day readmission (5.2% vs 7.3%, p=0.277) were similar in the two groups. Conclusions: On-table extubation is a safe and effective ERAS practice, that is associated with lower ICU LOS, postoperative LOS, and resource utilization, without affecting rates of reintubation, ICU readmission, 30-day readmission or operative mortality.
Abstract 14681: Quantitative Whole Blood Platelet Aggregation Predicts Occurrence of Subacute Thrombosis in Patients After Percutaneous Coronary or Peripheral Intervention
Authors: Nobusada Funabashi, Kazuo Misumi
Journal: Circulation (2022)

Introduction: The risk of subacute thrombosis (SAT) after percutaneous coronary intervention (PCI) or percutaneous peripheral intervention (PPI) is high if patients show high whole blood platelet aggregation. Hypothesis: For such high-risk patients, even though dual antiplatelet therapy is performed, whole platelet aggregation should be quantitated and if high, the indication for additional antiplatelet therapy determined. Methods: This is a retrospective analysis of 12095 stents from 12095 patients (9173 males; mean age 69±11 years; 9470 PCI, 2625 PPI). The whole blood platelet aggregatory threshold index (PATI; WBA-Neo; ISK, Osaka, Japan) was calculated. PATI was used to determine the minimum concentration of adenosine 5'-diphosphate causing a non-reversible aggregation of platelets and indicated platelet aggregation (range 0-8 μM). The higher the PATI, the lower the platelet aggregation. All patients received single or double antiplatelet drug therapy according to physician choice. Results: SAT occurred in 18 (0.19%) of 9470 patients after PCI and in 9 patients (0.34%) of 2625 patients after PPI. Of 9470 patients after PCI, total blood PATI was 4.40 in 18 patients with SAT and 7.00 in 9452 patients without SAT (P&lt;0.001). Of 2625 patients after PPI, the total blood PATI was 4.97 in nine patients with SAT and 6.39 in 2616 patients without SAT; the former was significantly lower than the latter (P&lt;0.001). We combined patients with PCI and PPI. PATI was divided into nine grades: 0-0.99, 1-1.99, 2-2.99. 3-3.99, 4-4.99. 5-5.99, 6-6.99, 7-7.99, and &gt;7.99. Of 12095 patients, if PATI was 0-0.99, the incidence of SAT was greatest at 1.89%. If PATI was &gt;7.99, the incidence of SAT was lowest at 0.09%. We divided 12095 patients into two groups: PATI of 0-4.99 (N=2229) and PATI of &gt;4.99(N=9866); the incidence of SAT was greater in the former (0.72%) than latter (0.11%; P&lt;0.001). No significant differences existed in the percentage of each coronary risk factor between patients with and without SAT after PCI, PPI, and PCI or PPI. Conclusions: In patients after PCI and/or PPI, despite single or double antiplatelet drug therapy, the whole blood platelet aggregation should be checked, and if PATI is 0-4.99 the indication for additional antiplatelet therapy should be considered.
Abstract 221: Machine Learning Algorithms For The Prognostication Of Return Of Spontaneous Circulation
Authors: Kiera Liblik, Quintyn Farrar, Steven Brooks, Akshay Rajaram
Journal: Circulation (2022)

Introduction: Several factors are known to influence return of spontaneous circulation (ROSC) following out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA). Machine learning (ML) methods are capable of analyzing large datasets to elucidate the clinical and prognostic value of specific variables. In cardiac arrest, ML may help identify predictors of ROSC in OCHA and ICHA. Purpose: The present systematic review summarizes the literature on ML algorithms used to predict ROSC in OHCA and IHCA. Methods: PubMed, EMBASE, Web of Science, and Cochrane were searched to identify articles. Studies on human subjects with OHCA or IHCA which used ML methods to predict ROSC were included. Results: A total of 4,094 studies were identified through a literature search. Ten were included in the final analysis with a total sample size of 240,798 patients (240,798 (93%) male). Studies used logistic regression (n=7), random forest models (n=2), or deep learning (n=1). Sociodemographic variables beyond age (n=8) and sex (n=5) were not used. Variables used for predicting ROSC included age (n=8), type of rhythm (n=7), witnessed arrest (n=5), and time to emergency services arrival (n=5). Most models were built using data from OHCA patients (n=7), with only three focused on IHCA. Studies utilized a variety of parameters for reporting the prognostic value of their models, including predictive accuracy (69%-99%), area under the receiver operating characteristic curve (0.71-0.83), sensitivity (50.2%-76.0%), and specificity (61.0%-92.9%). Conclusion: Despite the prevalence of cardiac arrest and advances in AI, only ten studies examined ML in the prognostication of ROSC. Logistic regression was predominantly used in the included studies, and there is a paucity of data on the efficacy of deep learning models. Furthermore, heterogeneity in the predictive efficacy of studied ML models merits additional work and the need for large-scale trials comparing ML to conventional methods and clinician judgment. Critically, there is also a need for greater data inclusivity in model development, understanding that marginalized populations are less likely to receive CPR.
Abstract 14566: The Role of Eosinophils in Pulmonary Hypertension
Authors: Ting Shu, Jiawei Zhang, Zhihua Chen, Yitian Zhou, Yanjiang Xing, Jing Wang, Chen Wang
Journal: Circulation (2022)

Introduction: Pulmonary hypertension (PH) is a severe life-threatening disease with insidious onset and high mortality, featured by pulmonary vascular remodeling and perivascular inflammatory cell infiltration. However, the precise immune mechanisms underlying PH remain unclear. Although an enhanced Th2 immune response in PH has been reported for years, the role of eosinophils (EOS), one of the Th2 effector cells, in PH is seldom reported. Investigating the roles and molecular mechanisms of EOS may present a novel paradigm of PH development. Hypothesis: EOS protect against PH through lipid metabolites. Methods: EOS infiltration and chemotaxis were investigated in peripheral blood and lung tissues from PH patients and sugen/hypoxia-induced PH mice. ΔdblGATA mice and anti-IL5 antibody (TRFK5)-treated mice were applied to investigate the role of EOS in PH development. Flow cytometry-based assays were used to quantify infiltration of different immune cells. The culture supernatants and lysates of EOS were collected to explore the mechanisms in co-culture cell experiments. Results: EOS accumulated in lung tissues from PH patients and mice, and the infiltration of EOS into pulmonary tissues during PH may be promoted by fibroblast-derived CCL11. Furthermore, EOS deficiency increased neutrophil (p=0.0038) and monocyte/macrophage (p=0.0344) infiltration and promoted pulmonary arterial smooth muscle cell proliferation, leading to aggravated PH in mice. Mechanistically, arachidonate 15-lipoxygenase (ALOX15), which catalyzes the production of pro-resolving lipid mediators, is specifically expressed by EOS. Conclusions: EOS play a beneficial role during PH development via ALOX15 and its downstream lipid mediators, suppressing perivascular inflammation and maintaining smooth muscle cell homeostasis.
Abstract 15393: Low Risk of Rheumatic Heart Disease Among Children Found to Have an Alternate Diagnosis to Acute Rheumatic Fever in a High Risk Setting
Authors: Jafesi Pulle, Emma Ndagire, Ndate Fall, Doreen Nakagaayi, Emmy Okello, Joselyn Rwebembera, Craig A Sable, Rachel Sarnacki, Scott Wirth, Jonathan Carapetis, Andrea Z Beaton
Journal: Circulation (2022)

Introduction: In 2015, the American Heart Association revised the Jones Criteria, the gold standard for diagnosis of acute rheumatic fever (ARF). This revision included changes to increase the sensitivity for ARF in high-risk settings. The objective of this study was to determine if there were children who were found to be ARF-negative by strict application of these criteria in a high risk setting but found to have rheumatic heart disease (RHD) on follow-up evaluation. Methods: Between 2017 and 2020, we conducted an epidemiological study to determine the incidence of ARF in Uganda. Children and adolescents, 3-17 years, presenting with clinical concern for ARF (fever and joint pain, suspicion of carditis, or suspicion of chorea) were enrolled and evaluated using the Jones Criteria. Children ultimately found to have a laboratory-confirmed alternate diagnosis and those who did not meet ARF criteria but had an unknown final diagnosis, were asked to participate in a longitudinal echocardiographic follow-up study to monitor for development of RHD. Presence of RHD was considered a false negative test and used to calculate the false negative error of not receiving a diagnosis of ARF. Results: There were 351 children determined to have an alternate diagnosis during the study period; 180 with a laboratory confirmed final diagnosis (127 malaria, 20 non-rheumatic cardiac disease, 15 influenza, 18 other) and 171 with an unknown final diagnosis. Of these, 220 (62.7%) had at least one follow-up visit (median 366 days, range 10-1054). One child (1/220, &lt;1%) developed echocardiographic evidence of borderline RHD during the follow-up period. Diagnostic overlap (met Jones Criteria but found to have a laboratory confirmed alternate diagnosis) was seen in 18% (33/180) of those with laboratory confirmed alternate diagnosis. Of these, 21 of 33 attended at least one follow-up (median 340 days, range 10-1054), and none showed echocardiographic evidence of RHD. Conclusions: Application of the 2015 Jones Criteria showed an exceptionally low rate of subsequent RHD, even in cases of diagnostic overlap. Clinicians working in ARF-endemic settings can have high confidence that children who do not meet criteria for ARF have a low risk of false negative diagnosis and short-term risk of RHD.
Abstract 14515: Initial Experience With Artificial Intelligence-Guided Echocardiography Acquisition in Rural America: Implementation and Quality Assessment
Authors: Michelle Kelsey, Gary Dunn, muchelle Duckworth, Alicia Provencher, Brenda Pattison, David Adams, Michael J Blaha, Matthew J Budoff, Susan Cheng, Ervin R Fox, Suzanne E Judd, Randolph Martin, Vasan S Ramachandran, James D Rhodes, Yngvil Kloster Thomas, James Thomas, Melissa A Daubert, Pamela S Douglas, Gerald S Bloomfield
Journal: Circulation (2022)

Background: Use of artificial intelligence-guided echocardiography (AI echo) may increase access to imaging, but there is little experience of its application in rural and low resource settings. The Risk Underlying Rural Areas Longitudinal (RURAL) cohort is the first NHLBI population-based cohort study to employ AI echo. Hypothesis: AI echo is feasible and produces adequate quality images to assess cardiac structure and function among rural populations. Methods: The RURAL study, in partnership with Caption Health (Brisbane, CA), is using AI echo in a multiethnic cohort of 4600 participants, performed in a mobile exam unit (MEU) in 10 rural U.S. communities. Non-sonographer MEU technicians underwent 10 hrs in-person competency-based training before scanning. Cardiac structure and function were analyzed in an independent core laboratory. Ejection fraction (EF) was visually estimated and calculated using Caption Health’s Auto EF technology. Results: Overall, 138 participants had AI echoes analyzed from Sept 2021 to May 2022 of whom 62% were women, with 70% obese (body mass index (BMI) ≥ 30kg/m 2 ), median BMI 33.8kg/m 2 (Table 1). Median time per scan was 20.0mins (15.5, 29.7). Image quality was adequate for visual EF in 97%, with left ventricular dimensions measurable in 88% and left atrial diameter in 91%. Adequate images of the right heart and ascending aorta were less common: base of the right ventricle measurable in 62%, right atrium 61% and ascending aorta 60%. Most participants (96%) had LVEF ≥ 50% by visual estimation, and there was 96% agreement between visual and Auto EF for this group. Image quality, but not measurability, varied with BMI. Conclusion: AI echo imaging technology can be used by non-sonographers to acquire adequate quality images characterizing cardiac structure and function in a rural and predominantly obese population, suggesting utility across the spectrum of BMI and applicability in low resource environments with limited access to healthcare.
Abstract 15805: Content Validity of a Measurement Tool to Assess Provider Concordance to the 2017 High Blood Pressure Clinical Practice Guidelines
Authors: Yacob Tedla, Philip Greenland, Christianne Roumie, David G Harrison, James Paparello, Joshua Beckman, James M Luther, Russell Rothman
Journal: Circulation (2022)

Introduction: The AHA/ACC 2017 High Blood Pressure clinical practice guidelines included numerous changes, including a new definition of hypertension (≥130/80 mm Hg) and lower thresholds for medication initiation, that may be challenging for clinicians to adopt. Developing and validating a tool to measure provider compliance to the guidelines is valuable for ascertaining compliance as a metric of healthcare quality. Methods: A five-step process was conducted. 1) Constructing items : 31 items that include five domains (screening, lifestyle, drug therapy, follow-up, laboratory) were compiled by the study investigators from the 2017 guideline. 2) Expert evaluation : A panel of five physicians with expertise in hypertension management reviewed and scored the items on how well they match to the guideline on a scale of 1 to 4 (1=does not match at all, 2=matches somewhat, 3=matches, 4=matches very well). The panel subsequently met face-to-face and came to a consensus on items that received &lt;3 score by any reviewer. 3) Refining items : Using information gathered during step 2, the tool was subsequently modified. 4) Expert reevaluation : experts rescored the match of the refined items to the guideline. 5) Validity score : Item Content Validity Index (I-CVI) was calculated as the proportion of experts who gave a score of ≥3 for an item and Scale Content Validity Index (S-CVI) as the proportion of items that received a score of ≥3 out of total items. I-CVI and S-CVI ≥0.80 were included in the final tool. Results: Twelve out of 31 items had a score of &lt;3 by at least one panel member. After the panel discussion, the contents of 9 of the 12 items were modified. The expert panel eliminated 2 of the 12 items because they were not clearly recommended in the guidelines. One item with ICV-I &lt;80% was eliminated. Each of the remaining 28 items had I-CVI ≥80% (10 had 80% and 18 had 100% I-CVI) and were included in the final tool. S-CVI for all items was 91%. Of 28 items, 3 were related to screening, 1 to lifestyle, 17 to drug therapy, 1 to laboratory, and 7 to follow-up. Conclusions: We developed and refined a measurement tool to evaluate provider level of compliance to hypertension treatment guidelines. This tool will be applied to identify patients at risk of receiving care inconsistent with current guidelines.
Abstract 15079: Sildenafil Promotes Mitochondrial Protein Deacetylation and Improves Mitochondrial Bioenergetics in Single Ventricle Congenital Heart Disease
Authors: Ashley E Pietra, Raleigh Jonscher, Genevieve Sparagna, ANGELA N BAYBAYON-GRANDGEORGE, Brian L Stauffer, Carmen C Sucharov, Shelley D Miyamoto, Anastacia M Garcia
Journal: Circulation (2022)

Introduction: Heart failure (HF) remains the leading cause of death and indication for transplant in single ventricle congenital heart disease (SV). Phosphodiesterase-5 inhibitors (PDE5i) are commonly used for the treatment of SVHF, with the primary target being the pulmonary vasculature. We have previously demonstrated that the failing SV heart is characterized by increased PDE5 activity and impaired mitochondrial function. We hypothesize PDE5i-mediated deacetylation of mitochondrial proteins via activation of sirtuin-3 (SIRT3) promotes enhanced mitochondrial bioenergetics. Methods: Mitochondrial bioenergetics were assessed using an Oroboros O2k high resolution respirometer on freshly explanted permeabilized myocardial tissue from 12 biventricular non-failing controls (BVNF), 21 SVHF, and SVHF hearts treated with PDE5i (n=14) or honokiol (a SIRT3 activator, n=5) for 40 minutes. We examined cardiac lysine acetylation in 8 explanted BVNF and 11 SVHF hearts and mitochondrial lysine acetylation in 2 SVHF samples +/-PDE5i via western blot. Statistical analysis was performed using unpaired Mann-Whitney tests between 2 groups and a Welch ANOVA with post-hoc Dunnett’s T3 multiple comparisons test for 3 group comparisons. Results: Mitochondrial function is impaired in SVHF compared to BVNF, but is rescued by treatment with PDE5i (A) and the SIRT3 activator honokiol (B). SVHF myocardial proteins are hyperacetylated compared to BVNF (representative blot, C, p=0.02). Treatment with PDE5i promotes deacetylation of mitochondrial proteins in failing SV hearts (representative blot, D). Conclusions: Mitochondrial bioenergetics may represent a novel therapeutic target for SVHF. Our data shows that failing SV hearts are typified by impaired mitochondrial function and protein hyperacetylation, and suggests that PDE5i improves mitochondrial function in SVHF through SIRT3 mediated deacetylation of mitochondrial proteins.
Abstract 15473: A New Metabolic Phenotype in a Mouse Model of Chronic Kidney Disease and Atherosclerosis
Authors: Mugdha V Padalkar, Ylona Gelfman, Mariya Kasiyanyk, Neil Kaungumpillil, Mohnish Singh, Eric Schram, Alexandra Tsivitis, Olga V Savinova
Journal: Circulation (2022)

Introduction: Patients with chronic kidney disease (CKD) experience significant cardiovascular morbidity and mortality. Vascular calcification is a hallmark of CKD and a strong predictor of atherosclerotic cardiovascular disease. Hypothesis: We hypothesize that CKD-induced vascular calcification potentiates atherosclerosis. Methods: First, wished to conduct a pilot study to confirm that a co-treatment of the low-density protein receptor mutant mice (Ldlr whc ) with a 0.2% adenine in a western diet will produce accelerated atherosclerosis, consistent with a well-known phenotype in the 5/6 nephrectomy model on an ApoE or Ldlr knockout background. Then we developed a two-step non-surgical mouse model in which the induction of calcification by a 0.2% adenine treatment was followed by western diet-induced hyperlipidemia. Results: Contrary to expected, the adenine and western diet (W+A) co-treatment resulted in a striking reduction of plasma triglycerides (TG), aortic root atherosclerosis, and liver lipids despite a fully penetrant CKD phenotype with tubulointerstitial damage, increased blood urea nitrogen, hyperphosphatemia, polyuria, vascular calcification, and osteoporosis. The two-step induction of CKD and atherosclerosis demonstrated partially normalized but reduced plasma triglycerides and liver lipid content, polyurea, and polydipsia in CKD mice, and there was no difference in atherosclerotic burden or plaque calcification between the groups. Interestingly we observed an increase in food and calorie intake and 24-hour glucose excretion in the urine in the pre-treated group compared with mice on a western diet without pre-treatment, while plasma glucose levels were not different between the groups. Conclusion: The paradoxical lack of dyslipidemia in mice treated with adenine provides an insight into the potential effects of tubulointerstitial kidney disease and nephrogenic diabetes incipits on lipid metabolism and atherosclerosis. 1